The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction.
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BACKGROUND/OBJECTIVES:Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes. DESIGN:Observational prospective cohort. SETTING:Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital. PARTICIPANTS:Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery. MEASUREMENTS:Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes. CONCLUSION:INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae.
Subjectand the INTUIT Investigators
Published Version (Please cite this version)10.1111/jgs.15770
Publication InfoBrowndyke, Jeffrey; Berger, Miles; Oyeyemi, Deborah; Olurinde, Mobolaji O; Whitson, Heather E; Weinhold, Kent J; ... Mathew, Joseph P (2019). The INTUIT Study: Investigating Neuroinflammation Underlying Postoperative Cognitive Dysfunction. Journal of the American Geriatrics Society. 10.1111/jgs.15770. Retrieved from https://hdl.handle.net/10161/17958.
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Associate Professor in Psychiatry and Behavioral Sciences
Dr. Browndyke is an Associate Professor of Geriatric Behavioral Health in the Department of Psychiatry & Behavioral Sciences. He also holds affiliate faculty appointments with the Duke Brain Imaging & Analysis Center (BIAC), Duke Institute for Brain Science (DIBS), Center for Cognitive Neuroscience (CCN), and the Duke Center for Geriatric Surgery. He has dual appointment to the Duke University Medical Center and the Durham VA Medical Center, the latter of which is where his c